title: Infectious precipitants of acute hyperammonemia are associated with indicators of increased morbidity in patients with urea cycle disorders.
abstract: OBJECTIVE
  To prospectively characterize acute hyperammonemic episodes in patients with urea cycle disorders (UCDs) in terms of precipitating factors, treatments, and use of medical resources.
  
  
  METHODS
  This was a prospective, longitudinal observational study of hyperammonemic episodes in patients with UCD enrolled in the National Institutes of Health-sponsored Urea Cycle Disorders Consortium Longitudinal Study. An acute hyperammonemic event was defined as plasma ammonia level >100 μmol/L. Physician-reported data regarding the precipitating event and laboratory and clinical variables were recorded in a central database.
  
  
  RESULTS
  In our study population, 128 patients with UCD experienced a total of 413 hyperammonemia events. Most patients experienced between 1 and 3 (65%) or between 4 and 6 (23%) hyperammonemia events since study inception, averaging fewer than 1 event/year. The most common identifiable precipitant was infection (33%), 24% of which were upper/lower respiratory tract infections. Indicators of increased morbidity were seen with infection, including increased hospitalization rates (P = .02), longer hospital stays (+2.0 days; P = .003), and increased use of intravenous ammonia scavengers (+45%-52%; P = .003-.03).
  
  
  CONCLUSIONS
  Infection is the most common precipitant of acute hyperammonemia in patients with UCD and is associated with indicators of increased morbidity (ie, hospitalization rate, length of stay, and use of intravenous ammonia scavengers). These findings suggest that the catabolic and immune effects of infection may be a target for clinical intervention in inborn errors of metabolism.
authors.affiliation: National Human Genome Research Institute, National Institutes of Health, Bethesda, MD. Electronic address: peter.mcguire@nih.gov.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: McGuire
authors.forename: Hye-Seung
authors.initials: HS
authors.lastname: Lee
authors.forename: Marshall L
authors.initials: ML
authors.lastname: Summar
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D022124:Hyperammonemia / Q000453:epidemiology / Q000209:etiology*; D007239:Infections / Q000150:complications*; D008297:Male; D015985:Precipitating Factors; D011446:Prospective Studies; D015996:Survival Rate; D056806:Urea Cycle Disorders, Inborn / Q000150:complications*
keywords: IV; Intravenous; LOS; Length of stay; OTC; Ornithine transcarbamylase; RDCRN; Rare Diseases Clinical Research Network; UCD; UCDC; Urea Cycle Disorders Consortium; Urea cycle disorder